The present manual inspection methodology for inspection of vials, containing pharmaceutical injectables, for particle contamination, involves a two step particle inspection sequence. The first step is the inspection of the container for black or dark particles in front of a flat white background which is used to optimize the contrast of black particles. The second inspection step occurs in front of a flat black background to improve the contrast and thus the detection for white particles. In both cases, the container is manipulated to induce motion in any suspended particles to permit the human eye to distinguish between stationary container defects and moving contaminating particles. In present practice, the container is moved about 8 to 12 inches between the white and black background inspection locations. Repositioning the inspected container requires both refocusing of the eyes and accurate repositioning of the inspector's head and the inspected container for each part of the inspection since the container is inspected at a near focus position, approximately 10 inches from the eye. These wasted motions reduce the rate at which an inspection of acceptable quality can be achieved. The energy lost in these non-productive motions result in deteriorated inspection performance due to the cumulative effect of inspector fatigue and can reduce inspector efficiency by as much as 30% at the end of a full work day, especially when a magnifying lens is used in the inspection. Repositioning can also vary the illumination available for inspection of the container, thereby introducing additional variability in the results of the inspection.
A light inspection booth used in the present manual inspection procedures for contaminating particles in pharmaceutical products, comprises of a 60 Hz ballast which excites a pair of 20 watt 11/2 inch diameter daylight fluorescent lamps. The fluorescent lamps are arranged in an open lighting fixture and are mounted 20 inches above (lateral positioning results in unwanted glare on the inspected container) the work surface. The booth can be used with or without a magnifying lens, which extends the visible range of the examined particles. Current illuminance recommendations for the aforementioned manual type of inspection recommend a minimum of 500 to a maximum of 1000 foot-candles, with a numerical mid-point value for the range being 750 foot-candles.
The inspection for contaminating particles in injectable solutions has been shown to be probabilistic in nature, and with inspection performed with a fluorescent light source, a rough relationship between the probability of detecting a particle in a container and the particle size has been established.
In the standardized inspection conditions employed (without a magnifying lens), a 50 .mu.m particle was not detected, a 100 .mu.m particle was detected 70% of the time and a 200 .mu.m particle was consistently detected 100% of the time. As the light intensity employed for the inspection is increased or the contrast of the particle increases, the detection probability is increased, with the corollary being that reduced light intensity and contrast results in decreased detection probability.
The target of the manual inspection therefore is the visible particle size range greater than 100 .mu.m. The experimental rejection probability for all particles in this size range evaluates the effectiveness of the manual inspection. Extensive biophysics literature on human vision has established that the light intensity used for the inspection and the contrast of the target against the background determine both the rate and the accuracy with which a critical inspection can be successfully accomplished. Conversely, the wider the latitude of the illuminance employed for the inspection, the more variable will be the results of a manual inspection. With uncontrolled luminance variation the position of the inspected container with respect to the light source can multiply the difficulty of obtaining a secure inspection for contaminating particles.
With present light sources, the light intensity at the inspection point varies with the size of the inspected container and its position with respect to the light source. These factors modify the illuminance available for inspection of contaminating particles and thus the security with which these particles are detected.
Current inspection booths have recently been modernized by replacing the two 20 watt lamps with a single 40 Watt 16 mm diameter hairpin lamp (e.g., G.E. F40/30BX/SPX/41RS or its Phillips equivalent PL-L 40W/30RS/41) in an open reflector. The variation of light intensity as a function of distance from the fluorescent lamp surface is overtly non-linear, which factor results in loss of detection security with extensive variations between similarly effected inspections.
Modernization with attempts to upgrade inspection reliability has generally focussed on enhancement of the degree of illumination and a flicker free source. No consideration has however been given to inspection condition variability which is the subject of the present invention.
An inspector's physical characteristics can have a profound effect on the results of a manual inspection. Thus, with an inspection position used by inspectors of standing heights ranging from 5' to 5'10", the variation in the inspection point for these inspectors, operating without a magnifying lens to define the inspection point, has been found to vary by as much as 8 inches. This 8 inch change in the position of the inspection point (relative to a stationary illumination source), results in a change in illuminance, at the spaced inspection points, for the inspection of the same container, by inspectors of different heights, of 652% (as shown from the .+-.4" range around the 8" illumination inspection distance of Table 1). The changing light intensity associated with the change in inspection position, especially of the magnitude described, contributes significantly to the variability of manual inspection results for the detection of particle contamination.
TABLE 1 ______________________________________ DISTANCE FROM RELATIVE RELATIVE LAMP SURFACE DISTANCE ILLUMINANCE INCHES R.sub.4 /R I/I.sub.4 ______________________________________ 4 1.00 1.0000 5 0.800 0.6833 6 0.666 0.3064 8 0.500 0.2093 10 0.400 0.1778 12 0.333 0.1533 14 0.286 0.1178 15 0.266 0.1047 16 0.250 0.0938 18 0.222 0.0767 20 0.200 0.0642 ______________________________________ Variation of light intensity with distance from an open luminaire equippe with two 16 mm 40 watt fluorescent lamps normalized to the light intensit 4 inches from the source. A change of .+-. 4 inches of the inspection point from the location 8 inches below the lamp surface changes the illuminance 652%.
To reduce the variability of human inspection results for contaminating particles in injectable fluids (or for that matter any type of similar illuminated inspection such as inspection for checking weld integrity and the like), the conditions under which the inspection is conducted must be defined and accurately controlled or contained.
It is therefore an object of the present invention to provide a method, and arrangement for effecting the method, whereby variability of manual inspection results are minimized for an inspection volume.
It is a further object of the present invention to reduce such variability with respect to pharmaceutical injectables.
It is yet another object of the present invention to provide an inspection station with means for quickly varying the background to white and black (for appropriate light and dark particle inspection respectively) to obviate the necessity for excessive movement of the object to be inspected to further reduce variability and inspector fatigue.
These and other objects, features and advantages of the present invention will become more evident from the following discussion.